title: Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study.
abstract: Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (βmeta = 0.2244 (standard error, 0.0548); P = 4 × 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (βmeta = -0.2796 (standard error, 0.0709); P = 8 × 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA. lpark@cc.hawaii.edu
authors.forename: Sungshim Lani
authors.initials: SL
authors.lastname: Park
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kucharska-Newton
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ambite
authors.forename: Christian P
authors.initials: CP
authors.lastname: Caberto
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Oetjens
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodloe
authors.forename: Shelly-Ann
authors.initials: SA
authors.lastname: Love
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D012307:Risk Factors
chemical_list: D004041:Dietary Fats; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: energy intake; fat mass and obesity-associated (FTO) gene; obesity; percent calories from fat; race/ethnicity